Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic
akita mice.
Authors Bugger H, Chen D, Riehle C, Soto J, Theobald HA, Hu XX, Ganesan B, Weimer BC,
Abel ED
Submitted By E. Dale Abel on 3/24/2010
Status Published
Journal Diabetes
Year 2009
Date Published 9/1/2009
Volume : Pages 58(9) : 1986 - 1997
PubMed Reference 19542201
Abstract OBJECTIVE: To elucidate the molecular basis for mitochondrial dysfunction, which
has been implicated in the pathogenesis of diabetes complications. RESEARCH
DESIGN AND METHODS: Mitochondrial matrix and membrane fractions were generated
from liver, brain, heart, and kidney of wild-type and type 1 diabetic Akita
mice. Comparative proteomics was performed using label-free proteome expression
analysis. Mitochondrial state 3 respirations and ATP synthesis were measured,
and mitochondrial morphology was evaluated by electron microscopy. Expression of
genes that regulate mitochondrial biogenesis, substrate utilization, and
oxidative phosphorylation (OXPHOS) were determined. RESULTS: In diabetic mice,
fatty acid oxidation (FAO) proteins were less abundant in liver mitochondria,
whereas FAO protein content was induced in mitochondria from all other tissues.
Kidney mitochondria showed coordinate induction of tricarboxylic acid (TCA)
cycle enzymes, whereas TCA cycle proteins were repressed in cardiac
mitochondria. Levels of OXPHOS subunits were coordinately increased in liver
mitochondria, whereas mitochondria of other tissues were unaffected.
Mitochondrial respiration, ATP synthesis, and morphology were unaffected in
liver and kidney mitochondria. In contrast, state 3 respirations, ATP synthesis,
and mitochondrial cristae density were decreased in cardiac mitochondria and
were accompanied by coordinate repression of OXPHOS and peroxisome
proliferator-activated receptor (PPAR)-gamma coactivator (PGC)-1alpha
transcripts. CONCLUSIONS: Type 1 diabetes causes tissue-specific remodeling of
the mitochondrial proteome. Preservation of mitochondrial function in kidney,
brain, and liver, versus mitochondrial dysfunction in the heart, supports a
central role for mitochondrial dysfunction in diabetic cardiomyopathy.

Investigators with authorship
E. Dale AbelUniversity of Iowa